Childhood Factors Associated With Unnatural Death Through Midadulthood

Key Points Question Which childhood factors are associated with death from unnatural causes (unintentional injury, suicide, and homicide) by midadulthood in an urban population-based cohort? Findings In this cohort study of 2180 participants, 10.2% of male participants had died by age 41 years. Only male sex and neighborhood poverty at ages 10 to 11 years remained significantly associated with unnatural death after controlling for other individual, family, and neighborhood factors. Meaning These findings suggest that to make long-term gains in reducing health disparities, efforts targeting concentrated neighborhood-level poverty in childhood should be a national priority.


Introduction
In 2021, life expectancy decreased in the US, especially among Black and Indigenous individuals. 1 Drug overdoses, homicide, suicide, and motor vehicle fatalities accounted for 31% of the decline in life expectancy from 2014 to 2021. 2,3Unintentional injury, suicide, and homicide, collectively termed unnatural deaths, remained the top 3 leading causes of death among those aged 15 to 34 years from 2001 to 2021, despite current preventive strategies. 46][7] In 2019, the total costs arising from unnatural deaths in the US were $4.2 trillion. 4,8From a Life Course-Social Field perspective, 9 incorporating factors from childhood from a variety of domains (eg, family, peers, and neighborhood), is vital for elucidating early targets for prevention.
The extant literature on factors associated with unnatural death is characterized by methodological limitations, such as a focus on high-risk populations, 10,11 which limits generalizability, and cross-sectional and retrospective studies, which are prone to recall bias. 12Although childhood is an important developmental period for lifelong health, 13 much etiological and intervention research is concerned with downstream risk factors more proximal to death.Few population-based prospective studies have examined childhood risk factors for unnatural death among urban samples of predominantly Black individuals, who are overrepresented in unnatural causes of death such as homicide. 14The suicide rate among Black individuals aged 10 to 24 years increased by 37% from 2018 to 2021, greater than any other racial or ethnic group. 15Research often focuses on specific types of unnatural deaths, despite evidence of shared risk factors across homicide, suicide, and overdose. 167][18][19][20][21][22] Friedman et al 20 followed the prospective cohort of Terman et al 23 of primarily White, gifted children growing up in California and found that childhood conscientiousness and social dependability were associated with longevity.Loeber et al 12 studied factors associated with homicide death in the Pittsburgh Youth Study and found that a combination of early behavior problems, large family size, and family relationship problems was associated with homicide.A prospective study of a birth cohort in Finland found that young male participants with divorced parents were more likely to die by unintentional injury or suicide after controlling for psychiatric diagnosis and parental social class. 24However, the number of deaths in these studies was quite small.Given the growing evidence that health outcomes are largely influenced by social determinants of health, 25 a major limitation of the current body of literature is the lack of focus on neighborhood and contextual influences 26 and the lack of inclusion of Black individuals.8][29][30] The aim of this study was to identify modifiable childhood risk factors for unnatural death using a social-ecological and life course framework 31 by including factors from several levels-individual, microsystem (family and peers), and mesosystem (neighborhood)-across several life stages (middle and late childhood and adolescence).

Methods
Data for this cohort study are from a group-randomized prevention trial 32,33 in 19 Baltimore City Public schools located in 5 distinct urban areas in East Baltimore, Maryland, that varied in sociodemographic factors and degree of racial segregation.All students in 2 cohorts of children entering first grade during the 1985 to 1986 (1196 students) and 1986 to 1987 (1115 students) academic years were randomized to 2 years of exposure to the Good Behavior Game, Mastery Learning intervention or the standard classroom setting (control condition).Childhood and adolescent assessments were conducted in grades 1 through 9. Baseline or childhood assessments were missing for 130 youths, and 1 child was excluded because of missing date of birth information (eFigure in Supplement 1).In young adulthood, 75% of the sample participated in a follow-up interview (ages 20-21 years).Death data were obtained from the National Death Index (NDI) Plus 34 through December 31, 2020, which provided linkage of study participants data to vital statistics data from the 50 states.The following identifiers were linked to the NDI: last name, first name, sex, date of birth, and Social Security number.The NDI provided multiple potential matches of deaths to each submitted person, and a scale ranking the quality of information was created, allowing us to limit matches according to quality.
Study protocols were approved by the institutional review board of Johns Hopkins University.
Parents provided written informed consent for data collection.Verbal assent was obtained from youths; after they reached adulthood, they provided written consent.This study followed Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. 35

Individual Factors Early Childhood
Sociodemographics (collected from school files in fall of first grade) included sex, race (Black or all other races), and free or reduced lunch status.Data on race were included to describe the demographics of the population; because Black individuals constituted the majority of the sample, we used this as one group and combined the rest of the sample.Teacher-rated aggressive behavior was assessed in the fall of first grade using the Teacher Observation of Classroom Adaptation-Revised. 36A trained interviewer administered this structured interview to the teacher, who was able to rate each child's performance in several domains.Ten items, rated on a scale from 1 (almost never) to 6 (almost always), comprised the aggressive-disruptive subconstruct: breaks rules, breaks things, harms others, harms property, fights, yells at others, lies, acts stubborn, teases others, and takes others' property.Children scoring in the top quartile were considered highly aggressive and disruptive.8][39] The Children's Depression Inventory contained 27 items on a scale of 0 to 2 assessing frequency of depressive symptoms in the past 2 weeks.The Revised Children's Manifest Anxiety Scale contained 37 yes-or-no items on the child's anxious feelings or actions.Items were summed for each scale, and children scoring above the median on both depressive and anxiety symptoms were classified as high depressed or anxious, consistent with prior research. 40

Later Childhood and Adolescence
Reported drug use was assessed from ages 9 to 14 years.Youths were asked whether they had ever used alcohol, cannabis, crack, cocaine, or sniffed any substance and, if so, age of first use.Because of the low prevalence of use of crack, cocaine, and inhalants, a 3-category variable was created to indicate early substance use (before age 15 years): no use, either alcohol or cannabis, or both alcohol and cannabis.

Household and Peer (Microsystem) Factors
Early Childhood Parents reported on household structure and highest level of education in the household in an interview in third grade.Household structure was characterized as having 1 adult in the home vs 2 or more.Education level was dichotomized into non-high school graduate vs high school graduate or higher.

Later Childhood and Adolescence
In fifth grade, deviant peer affiliation (defined as formation of attachments to deviant and substanceusing peers) 41 was measured through 5 standardized interview questions adapted from the Peer Behavior Scale, 42 and parental monitoring (defined as parental tracking of the child's whereabouts, activities, and adaptations) 43 was measured with 10 standardized questions adapted from the Parental Monitoring Scale. 42Children indicated the frequency with which their peers engaged in deviant behavior, such as substance use and antisocial activities, and the level of parent or guardian supervision.Total scores were created for both measures by summing responses.Higher scores indicate more deviant peer affiliation and more parental monitoring, respectively.

Neighborhood (Mesosystem) Factors in Later Childhood and Adolescence
Neighborhood rates of aggravated assault and public assistance were measured by 1990 US Census data and were used to describe neighborhood context when participants were aged approximately 10 to 11 years (grade 5 or 6).Raw data were transformed by taking the arcsine square root, owing to the small proportions after the data were weighted by the number of people within a Census tract, and then multiplying by 10.Intervention design status (control vs intervention) and cohort (1 or 2) were also included.

Outcomes
Cause of death was from the NDI and, when not available, death certificates were obtained.Deaths were classified according to manner of death categories-natural, unintentional injury, suicide, homicide, or undetermined-according to what was written on the death certificate and/or

International Classification of Diseases, Ninth Revision or International Statistical Classification of
Diseases and Related Health Problems, Tenth Revision (ICD-10) codes (eTable in Supplement 1).In this study, all undetermined deaths were classified as unnatural owing to notes on the death certificate indicating narcotic intoxication without clear evidence of suicide intent (15 deaths); however, 2 undetermined deaths, described as "subject ran over by train" and "gunshot wound to the head," were reclassified as suicides.

Statistical Analysis
Data analysis was performed from February to May 2023.Missing data on covariates ranged from 3% to 47% (median, 23%) and were multiply imputed simultaneously in R statistical software version 3.4.3(R Project for Statistical Computing) for all covariates in the final analytic sample using the multiple imputation by chained equations method 44,45 and package. 46Each covariate with missing values was modeled as a function of all other variables, plus the event indicator and estimated cumulative hazard, as recommended in White et al. 47 The number of iterations was set to 10, and the mean and SD plots were examined to ensure imputations converged.Ten imputed data sets were generated.
All covariates of interest were first analyzed independently.Kaplan-Meier curves were examined, log-rank tests computed, proportional hazard assumption evaluated, residual plots examined, and univariate Cox proportional hazards models were run to estimate the relative hazard of death.For all covariates, models were run with an interaction with time to assess whether the interaction should be included to account for nonproportional hazards.e Neighborhood rates of aggravated assault and public assistance were measured by 1990 US Census data and were used to describe neighborhood context when participants were aged approximately 10 to 11 years (grades 5 or 6).Raw data were transformed by taking the arcsine square root, owing to the small proportions after the data were weighted by the number of people within a Census tract, and then multiplied multiplying by 10. significantly increase the hazard of unnatural death.Being female was associated with a significantly reduced risk of death from unnatural causes, but having a high school or higher household education was not.However, after adjusting for individual-level factors, being female was the only significant protective factor.High aggression and household structure were no longer associated with hazard of death.Adding family and peer factors to the model eliminated free or reduced lunch status as a significant factor.In the final model, being female remained the only factor significantly associated with a reduced risk of mortality (hazard ratio, 0.13; 95% CI, 0.08-0.22),and neighborhood-level public assistance was the only factor significantly associated with increased risk of mortality (hazard ratio, 1.89; 95% CI, 1.09-3.30).

Discussion
In this cohort study, 10.2% of male participants had died by age 41 years.Similar numbers of male participants and female participants died of natural causes, but male participants were much more likely to die by unnatural causes, especially homicide.Several individual, family, and neighborhood factors were associated with unnatural death, but only male sex and Census tract-level concentration of poverty remained significantly associated with unnatural death after controlling for other factors.
Our finding that female sex is protective against unnatural death is consistent with national mortality data.In the US, male individuals accounted for 67% of the 224 935 preventable injury-related deaths in 2021. 49However, mechanisms underlying the gender gap in mortality are not fully understood.
Several biological and social mechanisms, as well as modifiable behaviors, such as the use of alcohol and drugs and violence, may account for much of the shorter life expectancy among men. 50Our findings that sociodemographic and community variables, rather than modifiable individual-level factors (eg, behavior), were independently associated with unnatural death is consistent with a prior study, 12 but longitudinal research identifying childhood factors associated with death is rare.
The current study offers several advantages.First, its longitudinal design allows for investigation of temporality, because we followed 2 cohorts of individuals for approximately 35 years (from ages 6 to 41 years).This is particularly important when looking at outcomes such as suicide or homicide, where recall bias can severely impact inferences through the use of proxy-based recall after death. 12Second, the sample was submitted to the NDI, with ICD-10 cause of death information obtained.Third, the sample originated from an urban area and included predominantly Black individuals, a population at increased risk of unnatural death. 14r results offer modest support for less traditional prevention approaches.As was pointed out by Rockett and colleagues, 51 current prevention initiatives in the US emphasize downstream approaches, such as identifying and treating people in crisis; however, without parallel national efforts to address upstream factors and inequity, including policies and programs directed at children living in a high concentration of poverty (eg, increasing the federal minimum wage and earned income tax credits), 52 life expectancy will likely continue to decline while costs and suffering associated with unnatural deaths will increase.Given the enormous costs and suffering associated with unnatural deaths, states should enact policy to address childhood poverty, as has been done in Maryland. 53,54In addition to strengthening economic supports, promoting connectedness and teaching coping and problem-solving skills have shown crosscutting benefits across violence and injury domains. 55,56In 2021, suicides and homicides reached record highs, and from 2019 to 2021, nearly all of the increases in the US homicide and suicide rates were explained by an increase in the use of firearms. 57Gun-related homicide and suicide rates increased by 44% from 2014 to 2021 3 ; in 2021, more than 47 000 US individuals died by firearms. 58States should implement evidence-based policies shown to reduce gun-related suicides, accidents, and homicides, 57 such as permit to purchase laws, 59 extreme risk protection orders, 60 and child access prevention laws. 61,62 Childhood Factors Associated With Unnatural Death Through Midadulthood JAMA Network Open.2024;7(2):e240327.doi:10.1001/jamanetworkopen.2024.0327(Reprinted) February 23, 2024 3/13 Downloaded from jamanetwork.comby guest on 02/29/2024 Lifetime exposure to assaultive violence (rape; sexual assault; shot or stabbed; mugged or threatened with a weapon; held captive, tortured, or kidnapped; and badly beaten) was retrospectively assessed in early adulthood (ages 20-23 years).Participants were asked to report the age of occurrence and frequency of each type of traumatic event.

Table 1 .
Children entered the analysis at approximately age 6 years in the fall of first grade.Robust SEs were clustered at the school-grade classroom level.Deceased participants exited the analysis at their date of death, with those dying of natural or unknown (missing) causes censored.In addition, 4 individuals with deaths before age 10 years were censored at date of death, all of which were due to unintentional injury.Alive participants were censored at either the age of last interview or the date through which NDI deaths were ascertained (December 31, 2020).The median (IQR) age at the time of NDI death ascertainment was 41.0 (40.5-41.6)years.Multivariable models were then run in the following order: including all individual-level factors as covariates, then adding in family and peer factors, and finally adding neighborhood-level factors, which resulted in the full, final model.All analyses were conducted using Stata statistical software version 14 (StataCorp) 48 using both the mi and st suite of commands for multiply imputed survival data.Statistical significance was assessed at the P < .05level, and all hypothesis tests were 2 sided.Vital Status and Cause of Death Categories in the Sample Overall and by Sex ResultsA total of 2180 participants (1090 female[50.0%];1461Black[67.0%]; 1168 receiving free or reduced lunch in the fall of first grade [53.6%]) (data not shown) were included in the analysis.The median (IQR) age in first grade was 6.3 (6.0-6.5)years.In total, 140 of 2180 participants (6.4%) died byDecember 31, 2020(Table 1), 110 (78.6%) due to unnatural causes, including 64 homicides (45.7%), 25 unintentional injuries (17.9%), 15 drug-related of undetermined intent (10.7%), and 6 suicides (4.3%).Two deaths were by unknown cause.The median (IQR) age of death was 27.7 (21.9-34.0)years and varied by cause of death (Table 2).Natural (median [IQR] age at death, 32.0 [26.4-35.4]years) and opioid-related (median [IQR] age at death, 31.7 [22.7-38.4]years) deaths occurred up to 10 years later than unintentional injuries (median [IQR] age at death, 23.5 [16.6-30.3]years), suicides (median [IQR] age at death, 24.1 [18.6-33.6]years), and homicides (median [IQR] age at death, 26.7 [22.2-31.9]years).Sex, free or reduced lunch status, and ever experiencing assaultive violence were significantly associated with cause of death.Male participants were significantly more likely than female participants to die (111 male participants [10.2%] vs 29 female participants [2.7%]; χ 2 1 = 51.3;P < .001)especially from unnatural causes (96 male participants [86.5%] vs 14 female a χ 2 1 = 51.3(P < .001).b Percentages are calculated using deceased participants as the denominator.c χ 2 1 = 16.1 (P < .001).

Table 2 .
Age at Death and Childhood Characteristics of Analytic Sample by Vital Status and Cause of Death a a Percentages for categorical variables with missing values do not include missing values.b Excludes 2 participants with unknown cause of death.c P values for continuous variables are from t tests or analysis of variance.d P values for categorical variables are from χ 2 tests.